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Article: Long-term carriers generate Epstein-Barr virus (EBV)-specific CD4 + and CD8 + polyfunctional T-cell responses which show immunodominance hierarchies of EBV proteins

TitleLong-term carriers generate Epstein-Barr virus (EBV)-specific CD4 + and CD8 + polyfunctional T-cell responses which show immunodominance hierarchies of EBV proteins
Authors
KeywordsEpstein-Barr virus
Immunodominance hierarchies
Lytic and latent proteins
Polyfunctional T cells
Issue Date2011
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/IMM
Citation
Immunology, 2011, v. 134 n. 2, p. 161-171 How to Cite?
AbstractT cells simultaneously producing multiple cytokines and possessing cytotoxic capacity termed polyfunctional cells (PFCs) are increasingly recognized as the immune correlate of protection against pathogenic viruses. We investigated co-expression of four cytokines (interferon-γ, macrophage inflammatory protein 1-α, tumour necrosis factor-α and interleukin-2) and degranulation capacity (CD107a surface expression) of Epstein-Barr virus (EBV) -specific CD4 + and CD8 + T cells upon stimulation by overlapping peptides of EBV lytic (BZLF1) and latent (EBNA1, EBNA3 and LMP2) proteins, in 20 healthy Chinese long-term carriers. Two patients with post-transplant lymphoproliferative disorder (PTLD), who had impaired T-cell immunity, were studied for comparison. Both EBV-specific CD4 + and CD8 + PFCs were readily generated in long-term carriers and showed immunodominance hierarchies of latent proteins (EBNA1>EBNA3/LMP2 and EBNA3>LMP2>EBNA1 for CD4 + and CD8 + T cells, respectively), as evidenced by a higher proportion of PFCs generated by immunodominant EBV proteins than by subdominant viral proteins. In contrast, the proportion of EBV-specific PFCs was markedly decreased in patients with PTLD. The EBV-specific PFCs produced more cytokine per cell than single-functional T cells and comprised different subsets. Five-functional CD4 + and CD8 + T cells were detected and four-functional CD4 + T cells were mainly CD107a negative and expressed all four cytokines whereas four-functional CD8 + T cells were mainly CD107a positive and expressed three of the four cytokines (interleukin-2-negative). We conclude that EBV-specific PFCs are generated in much higher proportions in the long-term carriers than in the patients with PTLD and maintain the immunodominant characteristics of the virus. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/143376
ISSN
2015 Impact Factor: 4.078
2015 SCImago Journal Rankings: 2.038
ISI Accession Number ID
Funding AgencyGrant Number
RGC-GRFHKU 763407M
CRCG10400665
Funding Information:

This work was supported by RGC-GRF grant (#HKU 763407M) and CRCG grant #10400665 of A. K. S. C. Part of this work was presented at the 14th Biennial Conference of the International Association for Research on Epstein-Barr Virus & Associated Diseases.

References
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DC FieldValueLanguage
dc.contributor.authorNing, RJen_HK
dc.contributor.authorXu, XQen_HK
dc.contributor.authorChan, KHen_HK
dc.contributor.authorChiang, AKSen_HK
dc.date.accessioned2011-11-24T10:04:22Z-
dc.date.available2011-11-24T10:04:22Z-
dc.date.issued2011en_HK
dc.identifier.citationImmunology, 2011, v. 134 n. 2, p. 161-171en_HK
dc.identifier.issn0019-2805en_HK
dc.identifier.urihttp://hdl.handle.net/10722/143376-
dc.description.abstractT cells simultaneously producing multiple cytokines and possessing cytotoxic capacity termed polyfunctional cells (PFCs) are increasingly recognized as the immune correlate of protection against pathogenic viruses. We investigated co-expression of four cytokines (interferon-γ, macrophage inflammatory protein 1-α, tumour necrosis factor-α and interleukin-2) and degranulation capacity (CD107a surface expression) of Epstein-Barr virus (EBV) -specific CD4 + and CD8 + T cells upon stimulation by overlapping peptides of EBV lytic (BZLF1) and latent (EBNA1, EBNA3 and LMP2) proteins, in 20 healthy Chinese long-term carriers. Two patients with post-transplant lymphoproliferative disorder (PTLD), who had impaired T-cell immunity, were studied for comparison. Both EBV-specific CD4 + and CD8 + PFCs were readily generated in long-term carriers and showed immunodominance hierarchies of latent proteins (EBNA1>EBNA3/LMP2 and EBNA3>LMP2>EBNA1 for CD4 + and CD8 + T cells, respectively), as evidenced by a higher proportion of PFCs generated by immunodominant EBV proteins than by subdominant viral proteins. In contrast, the proportion of EBV-specific PFCs was markedly decreased in patients with PTLD. The EBV-specific PFCs produced more cytokine per cell than single-functional T cells and comprised different subsets. Five-functional CD4 + and CD8 + T cells were detected and four-functional CD4 + T cells were mainly CD107a negative and expressed all four cytokines whereas four-functional CD8 + T cells were mainly CD107a positive and expressed three of the four cytokines (interleukin-2-negative). We conclude that EBV-specific PFCs are generated in much higher proportions in the long-term carriers than in the patients with PTLD and maintain the immunodominant characteristics of the virus. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.en_HK
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/IMMen_HK
dc.relation.ispartofImmunologyen_HK
dc.subjectEpstein-Barr virusen_HK
dc.subjectImmunodominance hierarchiesen_HK
dc.subjectLytic and latent proteinsen_HK
dc.subjectPolyfunctional T cellsen_HK
dc.titleLong-term carriers generate Epstein-Barr virus (EBV)-specific CD4 + and CD8 + polyfunctional T-cell responses which show immunodominance hierarchies of EBV proteinsen_HK
dc.typeArticleen_HK
dc.identifier.emailChiang, AKS:chiangak@hkucc.hku.hken_HK
dc.identifier.authorityChiang, AKS=rp00403en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1365-2567.2011.03476.xen_HK
dc.identifier.pmid21896011-
dc.identifier.scopuseid_2-s2.0-80052463886en_HK
dc.identifier.hkuros197754en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80052463886&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume134en_HK
dc.identifier.issue2en_HK
dc.identifier.spage161en_HK
dc.identifier.epage171en_HK
dc.identifier.eissn1365-2567-
dc.identifier.isiWOS:000295015000006-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectLongitudinal study of phenotypic changes and functionality of Epstein-Barr virus (EBV)-specific CD8+ T cell responses in symptomatic and asymptomatic EBV infection-
dc.identifier.scopusauthoridNing, RJ=54780334400en_HK
dc.identifier.scopusauthoridXu, XQ=54780939500en_HK
dc.identifier.scopusauthoridChan, KH=7406034307en_HK
dc.identifier.scopusauthoridChiang, AKS=7101623534en_HK
dc.identifier.citeulike9761506-

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